Newly-released Results from a Randomized and Controlled Study of the Ketogenic Diet in London

As many readers of Keto News may have heard from other media sources, a potentially very influential publication written by Dr. Liz Neal and her colleagues at the UCL- Institute of Child Health and Great Ormond Street Hospital, in London, England, was published in May in the medical journal Lancet Neurology. This study evaluated 145 children with intractable seizures and assigned half of the children to either receive the ketogenic diet for 3 months after a 4-week waiting period or after a 16-week period. This second group was therefore the control group – and was maintained on their usual medications.

Not surprisingly to those of us who have studied and used the ketogenic diet in our practices, the results were dramatic. There was a 38% decrease in the number of seizures in the children receiving the ketogenic diet after 3 months on the diet compared to a 37% increase in seizures for those who received medications as usual (the control group). Another way to look at this is the number of children who were "responders" (meaning children whose seizure counts were reduced by at least half during the study). In the ketogenic diet group, 38% were responders at 3 months, compared to only 6% in the control group. The response to the ketogenic diet is similar in magnitude, as the authors state, to what happens when new medications are given to a child who has severe epilepsy. The chances of a more impressive seizure reduction (>90% drop in seizures) was also significant: 7% with the ketogenic diet, 0% in those in the control group.

Although there was no true placebo (which would be no new therapy – or a "sugar pill" or in this case, "sugar diet"!), the waiting period was an effective way to create a control group, which had never been done before in a published study of a ketogenic diet. Many national guidelines require a blinded evaluation (in which the parent and/or the doctor are unaware if the child is receiving the treatment) to definitively prove that a treatment is effective. As one can imagine, this would be very hard to do for a dietary study. Most neurologists believe that the study of Dr. Neal and colleagues is a step in the right direction for ketogenic diet research to demonstrate to the general community (and insurance companies!) that this therapy truly works.

I had the opportunity to discuss the study results with Dr. Helen Cross, the senior author on this paper. Dr. Cross is a Professor of Neurology and Pediatric Epileptologist. She is also a well-respected world expert on the ketogenic diet and active on the scientific advisory board of Matthew's Friends.

Dr. Kossoff: "What impact do you think your study will have on the UK and the world?"

Dr. Cross: "I think it is already clear that however much we felt the ketogenic diet worked, to have a clear base of evidence is more convincing to both the original skeptics and managers alike. I can already see in the UK a realization that resources have to be provided."

Dr. Kossoff: "What have been the comments you've received from the UK and the world so far about your study? Has there been excitement? Or has it been more disbelief?"

Dr. Cross: "The comments so far have been encouraging and overwhelmingly supportive. Certainly most clinicians and parents are excited as their belief is that this will move the ketogenic diet further forward in the resource map in the treatment of epilepsy. In addition, comments about the study itself have also been very positive without any arguments about the specific data."

Dr. Kossoff: "How difficult was the study to do? Were parents willing to be randomized to the 16-week waiting group (compared to starting after 4 weeks)?"

Dr. Cross: "We had no problems recruiting; discussion in some cases did require time, most commonly when individuals were randomized to the control group. But when it was pointed out that they only had to wait an additional 12 weeks this didn't seem as bad as 3 months sounds. Also it had all been fully agreed and consents signed prior to randomization so we were dealing with disappointment rather than anything else - and of course here (at Great Ormond Street Hospital) it was still far sooner than they would get the diet anywhere else in the UK at the time."

The ketogenic diet for the treatment of epilepsy: a randomised, controlled trial.

Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, University College London, London, UK; National Centre for Young People with Epilepsy, Lingfield, UK.

BACKGROUND: The ketogenic diet has been widely and successfully used to treat children with drug-resistant epilepsy since the 1920s. The aim of this study was to test the efficacy of the ketogenic diet in a randomised controlled trial. METHODS: 145 children aged between 2 and 16 years who had at least daily seizures (or more than seven seizures per week), had failed to respond to at least two antiepileptic drugs, and had not been treated previously with the ketogenic diet participated in a randomised controlled trial of its efficacy to control seizures. Enrolment for the trial ran between December, 2001, and July, 2006. Children were seen at one of two hospital centres or a residential centre for young people with epilepsy. Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). Neither the family nor investigators were blinded to the group assignment. Early withdrawals were recorded, and seizure frequency on the diet was assessed after 3 months and compared with that of the controls. The primary endpoint was a reduction in seizures; analysis was intention to treat. Tolerability of the diet was assessed by questionnaire at 3 months. The trial is registered with ClinicalTrials.gov, number NCT00564915. FINDINGS: 73 children were assigned to the ketogenic diet and 72 children to the control group. Data from 103 children were available for analysis: 54 on the ketogenic diet and 49 controls. Of those who did not complete the trial, 16 children did not receive their intervention, 16 did not provide adequate data, and ten withdrew from the treatment before the 3-month review, six because of intolerance. After 3 months, the mean percentage of baseline seizures was significantly lower in the diet group than in the controls (62.0%vs 136.9%, 75% decrease, 95% CI 42.4-107.4%; p<0.0001). 28 children (38%) in the diet group had greater than 50% seizure reduction compared with four (6%) controls (p<0.0001), and five children (7%) in the diet group had greater than 90% seizure reduction compared with no controls (p=0.0582). There was no significant difference in the efficacy of the treatment between symptomatic generalised or symptomatic focal syndromes. The most frequent side-effects reported at 3-month review were constipation, vomiting, lack of energy, and hunger. INTERPRETATION: The results from this trial of the ketogenic diet support its use in children with treatment-intractable epilepsy. FUNDING: HSA Charitable Trust; Smiths Charity; Scientific Hospital Supplies; Milk Development Council.